The principal aim of the Washington University Alzheimer's Disease Research Center (ADRC) is to initiate, foster, and support the performance of innovative, cutting-edge research on Alzheimer's disease (AD) and related topics with regard to the etiology, pathogenesis, diagnosis, treatment, and prevention of disease. We accomplish this aim in a number of ways: by providing well-characterized research subjects (persons with AD and age-matched controls), their clinical and psychometric data, and their tissue (blood, DNA, CSF, autopsy material) to research projects;by providing intellectual and financial support to scientists at Washington University, at other Alzheimer's Centers, and the research community nationally and internationally;and by engaging in formal and informal collaborations, including multidisciplinary/ multi-Center studies and the initiatives sponsored by the National Institute on Aging, the National Alzheimer Coordinating Center, and the National Cell Repository for Alzheimer's Disease. Historically, our Center has focused on the earliest stages of dementia to identify the initial clinical and pathologic changes that distinguish AD from normal aging. Our approach is balanced between clinicopathologic and basic science domains with emphasis on interdisciplinary efforts. We will continue our training of students, fellows and junior faculty in clinical and basic science research skills. We will continue to engage in outreach activities to transfer information on AD to lay and professional audiences. We have a commitment to underserved populations that are the focus of our African American and Rural Satellites and will continue activities that promote the inclusion of these populations in research. This competing renewal application includes six cores: A: Administrative, B: Clinical, C: Data Management and Statistics, D: Neuropathology, E: Education and F: Genetics. There are two satellites: African American (Core B: Clinical) and Rural (Core E: Education). The ADRC resources contained in these Cores and Satellites will promote and advance AD-related research as represented by the three projects in this application: Project 1: Mapping substrate/gamma secretase interactions (R. Kopan);Project 2: Distinguishing aging and DAT effects on retrieval by fMRI (R. Buckner);Project 3: PET amyloid imaging in the elderly to evaluate DAT risk (M. Mintun).